TY - JOUR
T1 - Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows
AU - Zetterberg, Eva
AU - Vannucchi, Alessandro M.
AU - Migliaccio, Anna Rita
AU - Vainchenker, William
AU - Tulliez, Micheline
AU - Dickie, Renée
AU - Hasselbaich, Hans
AU - Rogers, Rick
AU - Palmblad, Jan
PY - 2007/5
Y1 - 2007/5
N2 - Background and Objectives: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from patients with myelofibrosis differed from that in samples from controls. Design and Methods: We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin). Results: In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (p<0.001) and vessels displayed 5.9-fold larger mean perimeters (p<0.001). MVD was 1.8-fold greater in JAK2 V617F-positive than in negative patients (p=0.026). Moreover, 92±11 % of vessels in patients with myelofibrosis were pericyte-coated but only 51±20 % of vessels in controls (p<0.001). In the two mouse models of myelofibrosis caused by targeting megakaryocytopoesis, wide, pericyte-coated and morphologically aberrant vessels were detected. MVD was significantly greater in bone marrow and spleen samples from animals with myelofibrosis than in wild-type mice. Interpretation and Conclusions: We conclude that angiogenesis is similarly abnormal in human and murine myelofibrosis with intense pericyte coating, presumably related to abnormal megakaryocytopoiesis.
AB - Background and Objectives: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from patients with myelofibrosis differed from that in samples from controls. Design and Methods: We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin). Results: In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (p<0.001) and vessels displayed 5.9-fold larger mean perimeters (p<0.001). MVD was 1.8-fold greater in JAK2 V617F-positive than in negative patients (p=0.026). Moreover, 92±11 % of vessels in patients with myelofibrosis were pericyte-coated but only 51±20 % of vessels in controls (p<0.001). In the two mouse models of myelofibrosis caused by targeting megakaryocytopoesis, wide, pericyte-coated and morphologically aberrant vessels were detected. MVD was significantly greater in bone marrow and spleen samples from animals with myelofibrosis than in wild-type mice. Interpretation and Conclusions: We conclude that angiogenesis is similarly abnormal in human and murine myelofibrosis with intense pericyte coating, presumably related to abnormal megakaryocytopoiesis.
KW - Angiogenesis
KW - Microvascular density
KW - Myelofibrosis
KW - Pericytes
KW - SMA
UR - http://www.scopus.com/inward/record.url?scp=34347393001&partnerID=8YFLogxK
U2 - 10.3324/haematol.11013
DO - 10.3324/haematol.11013
M3 - Article
C2 - 17488682
AN - SCOPUS:34347393001
SN - 0390-6078
VL - 92
SP - 597
EP - 604
JO - Haematologica
JF - Haematologica
IS - 5
ER -